Dual-HIV-regimen found to be a simple, safe salvage therapy

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The dual combination of dolutegravir (DTG) plus darunavir/ritonavir (DRV/r) provided a simple and safe salvage therapy to suppress viral replication without metabolic impact in patients infected with HIV-1, according to a retrospective-prospective observational study.

Researchers led by Amedeo F Capetti at the 1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Italy, identified 130 patients who were switched to a dual combination of DTG plus DRV/r and followed for a median of 56 months. Reasons that led to switching therapies included simplification, viral failure, toxicity, non-adherence, persistent low-level viremia, and drug-drug interactions. At baseline, 118 patients had drug resistance to between 1 and 5 antiretroviral classes, and virologic failure had occurred in 12 patients.

By week 48, 6.1% of patients had ongoing HIV replication compared with 40% at baseline, and 76.2% had an undetectable viral load compared with 38.5% at baseline. The success rate was 88.5% in patients who had active replication (³50 copies/mL) at baseline and 97.4% in patients who had ≤49 copies/mL at baseline.

Overall, 48% of baseline laboratory alterations returned to normal. By week 48, the proportion of patients with any metabolic alterations at baseline decreased for levels of serum glucose, creatinine, modified diet for renal disease of <90 mL/min, alanine aminotransferase, aspartate aminotransferase, triglycerides, and for total-, high-density lipoprotein-, and low-density lipoprotein-cholesterol.

Limitations of this study included poor patient selection criteria, which may have led to inclusion of a heterogeneous population.

“Switching to DTG plus DRV/r provided a simple and safe rescue regimen to all subjects, controlling viral replication in a high proportion of patients,” concluded the investigators. In addition, this treatment regimen demonstrated a positive metabolic effect in patients with metabolic alterations at baseline.

Background: Dolutegravir (DTG) plus darunavir/ritonavir (DRV/r) is a simple combination of drugs that has the best genetic barrier to HIV-1 resistance and may be fit for salvage therapy.
Methods: All HIV-1-infected subjects treated with DTG plus DRV/r between March 2014 and September 2015 in eight Italian centres were included in the analysis. The main metabolic data, efficacy parameters and safety data routinely collected were provided. This observational study is aimed to assess the efficacy of such approach. The primary end-point was the proportion of subjects achieving or maintaining virologic suppression <50 copies/mL at week 24. Secondary end points were maintaining virologic suppression in the follow-up (weeks 48 and 96) and safety.
Results: One hundred and thirty subjects were followed for a median of 56 months. Reasons for switching were simplification (44.6%), viral failure (30%), toxicity (16.9%), non-adherence (4.6%), persistent low-level viremia (3.1%), and drug-drug interaction (0.8%). At baseline, 118 subjects had documented resistance to 1 to 5 antiretroviral classes while 12 had viral rebound at a time when genotypic tests were not yet available.
Seventeen and 14 subjects took DRV/r and DTG twice daily, respectively. One subject was lost to follow-up, one discontinued for liver enzymes’ elevation, one died of illicit drug abuse and one of cancer-related complications.
The proportion of subjects with ongoing HIV replication dropped from 40% to 6.1%. Those with undetectable viral load increased from 38.5% to 76.2%. At week 48, 17.7% had HIV RNA between 1 and 49 copies/mL.
The number of subjects with altered serum glucose, creatinine, ALT, AST, total-, HDL- and LDL-cholesterol, triglycerides and MDRD <90 mL/min decreased by week 48, while those having MDRD <60 mL/min remained 4.6%. Overall 90/283 baseline laboratory alterations returned to normality.
Conclusions: Switching to DTG plus DRV/r proved to be safe, suppressing viral replication without metabolic impact.

Amedeo F Capetti, Maria Vittoria Cossu, Giancarlo Orofino, Gaetana Sterrantino, Giovanni Cenderello, Giuseppe V De Socio, Anna Maria Cattelan, Alessandro Soria, Stefano Rusconi, Niccolò Riccardi, Gian Maria Baldin, Fosca P Niero, Giorgio Barbarini, Giuliano Rizzardini

Infectious Disease Advisor report
BMC Infectious Diseases abstract

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